This application is generally in the field of methods and epidermal growth factor compositions for treatment of pulmonary hypoplasia in newborn infants.
The main problem with babies born prematurely is secondary pulmonary immaturity (hypoplasia). Persistent pulmonary hypertension of the newborn (PPHN) is the result of elevated pulmonary vascular resistance to the point that venous blood is diverted to some degree through fetal channels into the systemic circulation and bypasses the lungs, resulting in systemic arterial hypoxemia.
Before birth, a developing infant depends on the fetal circulation to supply oxygen and nutrients, then eliminate CO2 and other wastes via the placenta. The birth process causes dramatic changes in blood flow, bypassing the placenta, altering flow through the heart and major vessels, and opening the blood vessels within the lungs. With its first breath, an infant sets changes into motion which convert the circulatory system from that of an aquatic being to that of an air breather. As the lungs fill with air, resistance to blood flow through the lungs drops and normal blood flow begins. Two other important changes are the closure of the ductus arteriosus and of the foramen ovale. These two change the blood flow through the pulmonary artery and the heart respectively. If the changes above do not take place or only partially occur, it can create a condition known as persistent pulmonary hypertension or persistent fetal circulation.
Persistent pulmonary hypertension of the newborn is a pathophysiologic syndrome that results when the pulmonary vascular resistance fails to decrease after birth, despite improved alveolar oxygenation and lung expansion. Although systemic vascular resistance has increased (with the loss of the placenta), pulmonary vascular resistance remains equal to or greater than systemic vascular resistance. This results in blood continuing to flow through the foramen ovale and ductus arteriosus. Subsequently, with the loss of placental gas exchange and the inability to increase pulmonary blood flow, arterial oxygen tension falls to very low levels. If this situation is not reversed, the infant may die of severe hypoxemia.
Infants with persistent pulmonary hypertension are usually cyanotic with respiratory distress and tachypnea (fast respiratory rate). These infants need supplemental oxygen or, in severe cases, artificial ventilation. Diagnosis is usually confirmed by an echocardiogram which shows a large right-to-left shunting of blood through the heart and/or through a patent ductus arteriosus. Depending on severity, persistent pulmonary hypertension can quickly be fatal to a newborn. The most appropriate treatment of Persistent Pulmonary Hypertension of the Newborn remains unclear. Substantial variation in clinical practice exists between institutions. However, basic treatment goals do exist. In order of increasing aggressiveness and invasiveness: Improve alveolar oxygenation; Minimize pulmonary vasoconstriction; Maintain systemic blood pressure and perfusion; Induce an alkalotic state; Vasodilatation; Extracorporeal membrane oxygenation support. Medication, High Frequency Oscillatory Ventilation (HFOV), Inhaled Nitric Oxide (INO), and Extracorporeal Membrane Oxygenation (ECMO) are also some of the therapies used to manage these infants. HFOV is a unique type of ventilator that can increase oxygen in the blood without using high pressures that could effect pulmonary blood flow and damage the lungs themselves. INO is also delivered by a ventilator and acts as a vasodilator within the lungs opening blood vessels and reducing pulmonary blood pressures. ECMO actually acts as an artificial heart and lung, supporting blood pressure and oxygenation/ventilation.
It is readily apparent that additional, and better, treatments are needed.
It is therefore an object of the present invention to provide a treatment and compositions for treatment of pulmonary hypoplasia, and the complications associated with pulmonary hypoplasia.